A team of researchers led by Elizabeth Thiele, MD, PhD, director of the Pediatric Epilepsy Program at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, conducted a randomized, double-blind, placebo-controlled trial of cannabidiol with concomitant AED therapy in patients aged 2 to 55 years (34% over the age of 18) with treatment-resistant Lennox-Gastaut syndrome. Patients experienced at least 2 drop seizures per week at baseline and failure of treatment with at least 1 AED.

Over a 14-week period (with a 2-week dose escalation period), patients were randomly assigned to receive 20 mg/kg/d of cannabidiol in oral solution or placebo. Ultimately, 171 patients (mean age = 15 years; median drop seizure frequency = 74 per 28 days) were included in the trial; 86 received cannabidiol and 85 received placebo. Enrolled patients had previously been treated with a mean of 6 AEDs and received a mean of 3 concomitant AEDs during the trial.

Over the course of the treatment period, patients receiving cannabidiol experienced a median 44% reduction in monthly drop seizure frequency compared with 22% in patients who received placebo (P= .0135), with a difference in response notable within the first 4 weeks of stable dosing. This response was sustained through the end of the trial. Notably, 3 patients assigned to cannabidiol experienced no drop seizures during the maintenance period.

Adverse events, most of which were mild or moderate in the cannabidiol group, occurred in 86% of the cannabidiol group and 69% in the placebo group. The most common adverse events in the cannabidiol group were diarrhea, sleepiness, fever, decreased appetite, and vomiting. Serious adverse events, as determined by site investigators, including abnormal liver function (elevated LFT, but no clinical symptoms of toxicity), drowsiness, and loss of appetite, occurred in 20 patients in the cannabidiol group and 4 in the placebo group. These events were considered treatment related in 9 of the patients in the cannabidiol group, most of which were due to drug interactions. One death occurred in the cannabidiol group, though it was unrelated to treatment.

Overall, the results are promising, suggesting that cannabidiol is a safe and well-tolerated treatment for patients with Lennox-Gastaut syndrome whose drop seizures do not respond to standard AED therapy. “It is not a silver bullet, but there are children who benefit from this more than they have from other treatments,” Dr Thiele said in a statement.2